AB0646 G- CSF treatment for refractory digital ulcers in systemic sclerosis
Authors: S. Keret, G. Slobodin, A. Awisat, L. Kaly, I. Rosner, M. Rosenbaum, N. Boulman, A. Shouval, D. Rimar
Journal: Annals of the Rheumatic Diseases (2022)

Background Digital ulcers (DU) are a common manifestation of systemic sclerosis (SSc). Despite combination vasodilator therapy, refractory DU are not rare. Granulocyte-colony stimulating factor (G-CSF) had not been evaluated for SSc DU heretofore. Objectives To evaluate the efficacy and safety of G-CSF for refractory SSc DU. Methods Adult SSc patients with chronic resistant DU despite treatment with maximal tolerated doses of prostacyclin analogue, endothelin receptor antagonist and PDE5 inhibitor, were treated with three consecutive daily doses of G-CSF. Evaluation of DU healing, DUCAS score, antibiotics use, side effects and hospitalizations, was performed. Results Ten patients (90% females), mean age 53.5 ± 11.1 years were treated. Fifty percent of the patients had a diffuse SSc disease. All patients suffered from chronic (80%), or recurrent (20%) DU. G-CSF treatment resulted in complete resolution of most DU, after an average of 1.57± 0.76 months. DU recurrence occurred in two patients, after a mean period of two months. The number of DU decreased from 2.23±2.20 at baseline, to 0.84±0.80 at one month (p value= 0.04), and 0.50±0.67 at 3 months (p value= 0.015). DUCAS score dropped from 6.84±1.62 before the treatment, to 1.76±2.00 and 1.16±2.55 at one and three months, respectively (p value &lt;0.0001). No serious adverse events were observed. Conclusion G- CSF treatment was found to be beneficial for refractory SSc DU, resulting in DU healing and sustained remission in most cases. No significant side effects were observed. Future trials are needed to evaluate the efficacy and safety of this therapy. References [1]Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685-1699. [2]Mouthon L, Mestre-Stanislas C, Bérezné A, et al. Impact of digital ulcers on disability and health-related quality of life in systemic sclerosis. Annals of the Rheumatic diseases 2010; 69:214-217. [3]Hughes M, Pauling JD. Exploring the patient experience of digital ulcers in systemic sclerosis. Semin Arthritis Rheum. 2019;48(5):888-894. [4]Matucci-Cerinic M, Krieg T, Guillevin L, et al. Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry. Ann Rheum Dis. 2016;75(10):1770-1776. [5] Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology (Oxford). 2009;48 Suppl 3:iii19-24. [6]Roberts AW. G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors. 2005;23(1):33-41. [7]Phillipson M, Kubes P. The Healing Power of Neutrophils. Trends Immunol. 2019;40(7):635-647. [8]Giuggioli D, Magistro R, Colaci M, Franciosi U, Caruso A, Ferri C. The treatment of skin ulcers in systemic sclerosis: use of granulocyte-colony stimulating factor (G-CSF) in 26 patients. Reumatismo. 2006;58(1):26-30. Table 1. Patients’ characteristics: Parameter SSc IDU Mean age at DU onset (years) ±SD 53.5 ± 11.1 Female gender (N, %) 9, 90% Antibodies ATA (N, %) 3, 30% ACA (N, %) 5, 50% Negative 2, 20% Diffuse SSc subtype (N, %) 5, 50% Treatment (N, %) bosentan 10, 100% sildenafil 6, 60% CCB 2, 20% iloprost 10, 100% Mean Number of DU- baseline 2.23 ± 2.20 Mean Number of DU – 1 month ±SD 0.84 ± 0.80 Mean Number of DU – 3 months ±SD 0.50 ± 0.67 Mean DU duration before G-CSF (months)±SD 4.77 ± 4.53 Mean time to heal- (months)±SD 1.57 ± 0.75 Mean DUCAS before ±SD 6.84 ± 1.62 Mean change in DUCAS- 1M ±SD 5.07 ± 2.75 Mean change in DUCAS- 3M ±SD 5.58 ± 2.53 Adverse reactions (N, %) 0, 0% Abrreviations : SD- standard deviation, DU- digital ulcers, SSc- systemic sclerosis, ATA- anti topoisomerase antibodies, ACA- anti centromere antibodies, CCB- calcium channel blockers, G- CSF- Granulocyte-colony stimulating factor, DUCAS- digital ulcer clinical assessment score. Disclosure of Interests None declared